Different sensitivities of prostaglandin-cyclooxygenases in blood platelets and coronary arteries against non-steroidal antiinflammatory drugs.
The action of the non-steroidal antiinflammatory drugs indomethacin, tiaprofenic acid, diclofenac and meclofenamate on vascular and platelet-cyclooxygenases was studied by measuring the arachidonic acid-induced thromboxane A2 (TXA2)-formation of washed human platelets and prostacyclin (PGI2)-formation of bovine coronary artery rings. TXA2 was bioassayed as RCS on rabbit aorta strips, PGI2 in terms of its antiaggregatory activity on ADP-induced aggregation of human platelet-rich plasma. All of the substances studied produced concentration-dependent inhibition of PGI2- and RCS-release. The IC50 [micrometer] in inhibition of RCS-formation was 0.019 for indomethacin, 0.070 for tiaprofenic acid but 44.9 for meclofenamate and 63.2 for diclofenac. The IC50 [micrometer] in inhibition of PGI2-release was 0.42 for diclofenac, 0.63 for indomethacin and 0.99 for tiaprofenic acid. The data suggest (1) high sensitivity of human platelet-cyclooxygenase against indomethacin and tiaprofenic acid, (2) different sequence of the substances studied in inhibiting arachidonic acid-induced TXA2- and PGI2-formation. The possible therapeutic value of selective inhibition of platelets and vascular cyclooxygenases is discussed.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D013928:Thromboxane A2; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases